Osmoregulation occurs in all organisms, though the mechanisms differ according to the organism's environment. Fresh water inhabitants need to retain salts, whereas ocean inhabitants need to retain water. Terrestrial inhabitants need to conserve both water and salts. Organisms must balance these needs with a requirement to eliminate metabolic waste, such as nitrogenous waste, and generate secreted body fluids, such as saliva for digestion and sweat for thermoregulation.
In mammals, sweat glands, salivary glands, and the kidney all produce a primary secretion that is essentially isosmotic with blood and extracellular fluids. Modification of this primary secretion then occurs as much of the sodium chloride and water are reabsorbed as they pass through the excretory ducts of the glands and kidney, whereas potassium and bicarbonate ions are secreted. This modification of the primary secretion is important in the sweat glands to conserve sodium chloride in hot environments, and in the salivary glands to conserve sodium chloride when excessive quantities of saliva are lost. This modification is critical in the kidney to maintain proper sodium and water balance in the extracellular fluids, a balance which also regulates arterial pressure. Loss of this modification activity by the duct cells causes a large loss of sodium and water, resulting in severe dehydration and low blood volume, and ultimately to circulatory collapse.
Sodium absorption by the intestines, especially in the colon, is necessary to prevent loss of sodium in the stools. The loss of sodium absorption produces a failure to absorb anions and water as well. The unabsorbed sodium chloride and water then lead to diarrhea, with further loss of sodium chloride from the body. Other body fluids may be under regulation similar to that seen in the systems described above. For example, cerebrospinal fluid is produced by active sodium ion transport from the capillaries across the epithelium of the choroid plexus, which in turn attracts chloride ions and water. A counter flow of potassium and bicarbonate ions move out of the cerebrospinal fluid into the capillaries. A dysfunction in osmoregulation is associated with several disease states, including hyponatremia, renal failure, and hypernatremia. (Strange, K. (1992) J Am. Soc. Nephrol. 3:12-27.)
In insects, a system of osmoregulation similar to that in mammals exists. The malpighian tubules are blind-ended sacs extending from the juncture of the midgut and hindgut into the fluid-filled body cavity, the hemocoel. Active transport of potassium ions from the body fluid, the hemolymph, with passive diffusion of other ions and solutes, into the lumen of the malpighian tubule produces a urine essentially isosmotic relative to hemolymph. The urine then passes into the gut, where selective, controlled reabsorption of essential solutes and most of the water occurs in the anterior (ileum) and posterior (rectum) hindgut.
The insect ileum is functionally analogous to the proximal tubules of the vertebrate kidney. Reabsorption of fluids occurs due to active transport of chloride and sodium ions, with a passive flow of potassium ions, from the ilium to the lumen of the malpighian tubule. Also, hydrogen ions and NH.sub.4.sup.+ secretion, associated with bicarbonate absorption, contributes to pH regulation and nitrogen excretion by mechanisms which are analogous to those in the vertebrate kidney proximal tubules. (Ring, M. et al. (1998) Insect Biochem. Molec. Biol. 28:51-58.) A neuropeptide secreted by the corpus cardiacum in the locust Schistocerca gregaria appears to regulate ileal ion transport. The ion transport peptide (ITP), at picomole levels, fully stimulates Cl, Na.sup.+, and K.sup.+ movement and fluid reabsorption in the locust ileum. ITP also inhibits ileum acid secretion almost completely. Cyclic adenosine monophosphate (cAMP) also can stimulate ion movement and fluid reabsorption in the locust ileum, suggesting that ITP may work through this second messenger. (Meredith, J. et al. (1996) J. Exp. Biol. 199:1053-1061.)
ITP is produced as a prepropeptide of 130 amino acids. Cleavage of the first 55 N-terminal amino acids and the last C-terminal amino acid results in the native ITP molecule. ITP has considerable sequence similarity to a family of crustacean hormones including the crustacean hyperglycemic hormone (CHH), molt inhibiting hormone (MIH), and vitellogenesis-inhibiting hormone (VIH). ITP shows 42% homology with CHH. ITP and CHH also share six conserved cysteine residues common to all of the crustacean hormone family members and a potential amidation site at the C-terminal end of the molecule. Cleavage of the C-terminal end followed by amidation of the carboxyl group is a common maturation pathway for physiologically active peptides. (Meredith, supra; Soyez, D. (1997) Annals N Y Acad. Sci. 814:319-323.)
The discovery of a new human ion transport-like protein and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, treatment, and prevention of osmoregulatory and inflammatory disorders.